+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity



Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity



Pharmacology and Therapeutics 197: 122-152



Individuals differ substantially in their response to pharmacological treatment. Personalized medicine aspires to embrace these inter-individual differences and customize therapy by taking a wealth of patient-specific data into account. Pharmacogenomic constitutes a cornerstone of personalized medicine that provides therapeutic guidance based on the genomic profile of a given patient. Pharmacogenomics already has applications in the clinics, particularly in oncology, whereas future development in this area is needed in order to establish pharmacogenomic biomarkers as useful clinical tools. In this review we present an updated overview of current and emerging pharmacogenomic biomarkers in different therapeutic areas and critically discuss their potential to transform clinical care. Furthermore, we discuss opportunities of technological, methodological and institutional advances to improve biomarker discovery. We also summarize recent progress in our understanding of epigenetic effects on drug disposition and response, including a discussion of the only few pharmacogenomic biomarkers implemented into routine care. We anticipate, in part due to exciting rapid developments in Next Generation Sequencing technologies, machine learning methods and national biobanks, that the field will make great advances in the upcoming years towards unlocking the full potential of genomic data.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066444587

Download citation: RISBibTeXText

PMID: 30677473

DOI: 10.1016/j.pharmthera.2019.01.002


Related references

Genetic and/or non-genetic causes for inter-individual and inter-cellular variability in transporter protein expression: implications for understanding drug efficacy and toxicity. Expert Opinion on Drug Metabolism and Toxicology 11(12): 1821-1837, 2015

Inter-individual differences of 4- -phenylmethoxy-1-piperidinylbutyric acid disposition in rats Possible involvement of genetic polymorphism. Drug Metabolism & Disposition 22(5): 761-769, 1994

Inter-individual differences of 4-(4-(4-methylphenyl)-phenylmethoxy-1-piperidinyl)butyric acid disposition in rats: Possible involvement of genetic polymorphism. Drug Metabolism and Disposition 22(5): 761-769, 1994

Inter-individual differences of 4-[4-(4-methylphenyl)-phenylmethoxy-1-piperidinyl]butyric acid disposition in rats: possible involvement of genetic polymorphism. Drug Metabolism and Disposition: the Biological Fate of Chemicals 22(5): 761-769, 1994

Intraspecies differences in frequency of genes directly affecting drug disposition: the individual factor in drug response. Pharmacological Reviews 30(4): 555-563, 1978

Metabolism of drugs of abuse: its contribution to the toxicity and the inter-individual differences in drug sensitivity. Journal of Health Science 51(1): 1-7, 2005

Inter-individual differences in response to cardiovascular drug therapy. Medical Journal of Malaysia 43(1): 14-20, 1988

Inter-individual differences in metabolism of drugs: the role of genetic factors. Acta Pharmacologica et Toxicologica 29(Suppl. 3): 156-163, 1971

Factors determining the inter individual differences in dose requirement of the oral anti coagulant drug phenprocoumon. Naunyn-Schmiedeberg's Archives of Pharmacology 319(Suppl.): R83, 1982

Identification of genetic differences in drug metabolism: prediction of individual risk of toxicity or cancer. Hepatology 14(2): 398-401, 1991

Studies upon resistance factors in the mammary gland of the cow. I. Inter-individual differences in response to experimental infection caused by Streptococcus agalactiae. Prace i Materialy Zootechniczne (2): 59-72, 1973

Inter-individual differences of (+)-4-[4-(4-methylphenyl)phenylmethoxy-1-piperidinyl]butyric acid ((+)-MPPB) disposition in rats. Biological and Pharmaceutical Bulletin 16(10): 1057-1059, 1993

Genetic and epigenetic determinants of inter-individual variability in responses to toxicants. Current Opinion in Toxicology 6: 50-59, 2017

Sex-Specific Associations Between Inter-Individual Differences in Heart Rate Variability and Inter-Individual Differences in Emotion Regulation. Frontiers in Neuroscience 12: 1040, 2018

Individual differences in the pharmacokinetics of monomethylated tricyclic antidepressants: role of genetic and environmental factors and clinical importance. Annals of the New York Academy of Sciences 179: 739-751, 1971